The pharmacokinetics of subcutaneously injected bimosiamose disodium in healthy male volunteers

Abstract

Bimosiamose is a novel synthetic pan-selectin antagonist developed for the treatment of acute and chronic inflammatory disorders. Therefore the pharmacokinetics of Bimosiamose disodium were studied in healthy male volunteers after single and multiple subcutaneous injections. A randomized, double-blind, placebo-controlled dose escalation trial was carried out. The subjects received subcutaneous injections of placebo or 100, 200 or 300 mg Bimosiamose disodium into the abdomen. Plasma and urine concentrations of Bimosiamose were determined. The maximum plasma concentration was 2.17+/-0.70 microg/ml and the AUC(0-infinity) 11.1+/-2.9 h microg/ml after the highest dose on day 1 (mean+/-SD). For the apparent clearance CL/f 28.7+/-7.3 l/h and the terminal half life t(1/2) 3.7+/-0.6 h were calculated. The mean residence time MRT(infinity) of 5.5 to 6.3 h for s.c. injection exceeded that after i.v. infusion due to an extended absorption time. For multiple dosing, constant pre-dose concentrations of about 20 ng/ml may be reached after two subsequent doses of 200 or 300 mg Bimosiamose disodium once daily. Almost 15% of the administered drug was excreted unchanged in urine. Moreover, Bimosiamose was well tolerated.

The engagement of selectins and their ligands in colorectal cancer liver metastases

“…2) is a pan‐selectin synthetic antagonist and the leading selectin inhibitor in clinical development. It has been tested in animal models and human beings for inflammatory diseases, such as asthma and chronic obstructive pulmonary disease, with favourable results and low toxicity [70–72]. Heparin also exerts anti‐inflammatory as well as anti‐metastatic effects, partly inhibiting L‐ and P‐selectin binding.…”